JÖRG TATZELT



ABERRANT PROTEIN FOLDING AND NEURODEGENERATION


Various approaches coming from neuropathology, genetics, animal modeling and biophysics have established a crucial role of protein misfolding in the pathogenic process of different neurodegenerative diseases, such as Alzheimer's disease, Parkinson’s disease, polyglutamine expansion diseases and prion diseases. However, there is an ongoing debate about the nature of the harmful proteinaceous species and how toxic conformers selectively damage neuronal populations.

The main aim of our biochemical research is to identify cellular factors and signaling cascades implicated in neuronal integrity and in the pathophysiological alterations leading to neurodegeneration. Our integrative research has a strong focus on the biochemical and cell biological analysis of cellular pathways, which are also of broad neurobiological interest. Specifically, we are employing in vitro, yeast, neuronal cell culture and animal models to focus on three major topics:

  • Cellular mechanisms underlying the formation and toxic activity of aberrant protein conformers
  • Signaling pathways induced by neurotoxic conformers
  • Therapeutic strategies for neurodegenerative diseases

SELECTED PUBLICATIONS


link to PubMed


Gonsberg et al. (2017). The Sec61/SecY complex is inherently deficient in translocating intrinsically disordered proteins. J Biol Chem, Epub ahead of print.

Eigenbrod et al. (2017). Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice. PLoS One, 12(12):e0188989. doi: 10.1371/journal.pone.0188989.

Wu et al. (2017). The N-terminus of the prion protein is a toxic effector regulated by the C-terminus. Elife, 6: doi: 10.7554/eLife.23473.

Puig et al. (2016). Secretory pathway retention of mutant prion protein induces p38-MAPK activation and lethal disease in mice. Sci Rep, 6: 24970.

Woerner et al. (2016). Cytoplasmic protein aggregates interfere with nucleo-cytoplasmic transport of protein and RNA. Science, 351(6269): 173-176.

Meka et al. (2015). Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration. J Clin Invest., 125(5): 1873-1885.

Pfeiffer et al. (2013). Structural features within the nascent chain regulate alternative targeting of secretory proteins to mitochondria. EMBO J, 32: 1036-1051.

Resenberger et al. (2011). The cellular prion protein mediates neurotoxic signaling of ß-sheet-rich conformers independent of prion replication. EMBO J, 30: 2057-2070.